Carbohydrate Metabolism Pt. 1 Flashcards
What cells in our body undergo glycolysis?
All cells in our body undergo glycolsis
Can other monosaccharides enter glycolysis?
Yes. Fructose and galactose
Glucose is super important for the ________ and ________.
- RBCs
2. Brain
Why is glucose important for the brain?
In NON-STARVING conditions, glucose is the only fuel that the brain uses.
Where can we get our sources of glucose from?
- Monosaccharides like glucose, fructose and galactose
2. Disaccharides like [sucrose] and [lactose]
Sucrose, a disaccharide, can be broken down into ______ and _____ via
glucose
fructose
via sucrase
Lactate, a disaccharide, can be broken down into _____ and _____ via
glucose
galactose
via lactase
Gluconeogenesis in the liver called what?
De novo synthesis.
Why do RBC need glucose to survive?
Their only source of NRG is glucose. They do not have MT to make any other kinds of NRG.
When there is a defect in glycolysis, what cells suffer the most?
- RBCs and
2. Brain
Can glucose diffuse into cells?
No. It is polar. It needs the help of GLUT transporters
GLUT1
Location:
Affinity:
Km:
GLUT1 are found everwhere, but mainly the heart and the brain.
High affinity
Low Km
GLUT2
Location:
Affinity:
Km:
Liver
Low affinity
High Km
GLUT 3
Location:
Affinity:
Km:
Neuron
High affinity
Low Km
GLUT4
Location:
Affinity:
Km:
GLUT4
Location:
skeletal muscle
fat and
heart
TRICK: GLUT4 are special because they are insulin-dependent.
When glucose is high, insulin binds to receptors on a enzyme. Usually, GLUT4 receptors are stored in vesicles in the cell. So when insulin binds, this signals for GLUT4 receptors to be placed in the membrane.
Before we begin glycolysis: what is the strategy in glycolysis and the TCA cycle?
We want to HARNESS chemical NRG.
The more that carbon is reduced (gaining H and electron; losing O), the more NRG that it can have. Why? Because when Carbon is oxidized (gains an oxygen or loses H/electrons), NRG is released.
ATP can be formed by substrate-level phosphorylation from high energy compounds like ______ and ______
13BPG and
PEP
Oxidation
Gain O
Lose H/electrons
Reduction
Gain H/electrons
Lose O
What is SLP?
SLP is when we make ATP from ADP by transferring a phosphate.
What 2 intermediates in glycolysis undergo SLP?
- PGK [1,3 BPG–>3PG]
2. Pyruvate kinase
In glycolysis, in all steps that involve ATP, what cofactor is needed?
Mg2+
What in glycolysis generates the first high NRG intermediate?
GAP3DH creates NADH.
____ is the NRG money of the cell. Why?
NADH.
NADH stores NRG as 2 electrons, which can then be taken to the ETC
Catabolic pathways do what?
Catabolic pathways break down via
EXERGONIC, OXIDATIVE to make ATP
Anabolic pathways do what?
Anabolic pathways BUILD UP via
endergonic, reductive reactions.
What is the net yield of glycolysis?
4 energy molecules total:
- 2 ATP
- 2 NADH
Where does anaerobic glycolysis occur?
RBC and overworked muscle
What happens in anaerobic glycolysis?
Pyruvate–> lactate.
How can we remove lactic acid in overworked muscle or RBC when it is too much?
Cori cycle.
3 phases of glycolysis:
- Investment- need 2 ATPs
- Splitting
- Recoup- 2 ATP and 2 NADH
Investment phase important enzymes
- Hexokinase/glucokinase: Glu–>G6P
- F6P–> F16BP: PFK1
* main regulatory step
Why is it called the investment phase?
2 ATP are needed
In any step in glycolysis that involves ATP, we need what cofactor?
Mg2+
What is the main regulatory step of glycolysis?
PFK1.
Where is hexokinase located?
All cells
Where is glucokinase located?
Liver
Pancreatic B cells.
What do hexokinase and glucokinase do to glucose?
They phosphorylate glucose. When glucose is phosphorylated, it is locked in the cell.
What regulatory effect does an increase of G6P have?
Inhibits HEXOKINASE. Not glucokinase!
What regulatory effect does an increase of glucose, insulin and F1P have?
Promote glucokinase in the liver and pancreatic B cells.
What regulatory effect does F1P have?
It promotes the activity of glucokinase in the liver and pancreatic B cells.
What regulatory effect does ATP and citrate have on PFK?
inhibit
What regulatory effect does AMP and F26BP have on PFK?
Promote PFK.
Important Recoup phases
- Glyceraldehyde 3 phosphate–> 1,3 BPG via [GAP3DH]
- 1,3BPG–> 3PG via [PGK]
- PEP–> Pyruvate kinase via [Pyruvate kinase]
What does GAP3DH do?
GAP3DH is an enzyme that converts G3P–> 1,3 BPG.
In this process, a NAD+ is reduced to NADH (electrons are gain). RMBR that NADH has a high amount of NRG. So, it will later be oxidized in the oxphos.
What does PGK do?
PGK- phosphoglycerate kinase
PGK converts 1,3BPG to 3PG. ADP is phosphorylated to ATP: creating the first ATP!
Remember this is SLP.
Pyruvate kinase
PEP–> Pyruvate,
Creating a ATP.
3 checkpoints in glycolysis
Checkpoints are what make the process irreversible. They have a very high -deltaG.
- hexokinase/glucokinase
- PFK
- Pyruvate kinase.
The activity of the 3 checkpoints are influenced by 5 things. What are these 5 things?
- ATP
- AMP
- Glucose
- Insulin
- Glucagon
Hexokinase/glucokinase is inhibited by G6P.
Hexokinase is inhibited by G6P.
Glucokinase is NOT inhibited by G6P.
2 things phosphorylate glucose. What are they?
hexokinase and
glucokinase.
BUT: they’re found in different parts of the body so they have different kinetics.
Hexokinase
Location:
Affinity for glu:
Km:
All cells.
High affinity for glucose
Km-low
Glucokinase
Location:
Affinity for glu:
Km:
Liver and pancreatic B cells.
Low affinity for glucose
high Km–> because does not want to bind
Why it glucokinase’s affinity for glucose less?
because it has to be more selective.
High amounts of ______ tells the cell to transfer glucokinase to the nucleus.
F6P.
Because when there is a buildup of F6P, something is wrong with glycolysis so we want to stop it,
PFK-1 is activated by:
- AMP
2. F26BP
Why is PFK-1 promoted when F26BP is present?
F2,6BP activates PFK1 because it is a side reaction that basically controls PFK1. PFK2 will produce F26BP, which then turns on PFK1.
Remember we said that 3 control points are regulated by ATP, AMP, ______, _______ and glucose
insulin and glucagon
What effect does high insulin/low glucagon have on PFK1.
High insulin/low glucagon means that we are in a FED state.
Insulin will activate PFK1.
What mechanism does insulin activate PFK1?
When insulin is present, [phosphotases] will be activate. Phosphotases will [remove a phosphate] from PFK2. When PFK2 is de-phosphorylated, it is actually activated. Thus, PFK2 will produce F26BP, which will activate PFK1.
What effect does low insulin/high glucagon have on PFK1?
inhibit PFK1.
What mechanism does glucagon inhibit PFK1?
When glucagon is present, [kinases] will be activated.
Kinases will phosphorylate PFK2, shutting it down and STOPPING the making of F26BP.
What mechanism does glucagon inhibit PFK1?
When glucagon is present, [kinases: CaMP] will be activated.
Kinases will phosphorylate PFK2, shutting it down and STOPPING the making of F26BP.
When ______ is high, phosphotases will be activated to dephosphorylate PFK2, activating PFK1.
Insulin
When ____ is high, kinases will be activated to phosphorylate PFK2, inhibiting PFK1.
Glucagon
What regulators will activate [pyruvate kinase]?
Insulin
F16BP
What regulators will activate [pyruvate kinase]?
- Insulin
2. F16BP***
What regulators will inactivate [pyruvate kinase]?
- ATP
- Glucagon
- Alanine***
How does insulin act on pyruvate kinase?
Insulin works on [pyruvate kinase] in the same method as PFK2.
Insulin activates phosphotases, de-phosphorylating pyruvate kinase, which ACTIVATEs it.
How does glucagon act on pyruvate kinase?
Glucogon works on [pyruvate kinase] in the same method as PFK2.
Glucagon activates kinases (cAMP), which phosphorylate pyruvate kinase, which INHIBITS it.
Pyruvate kinase is activated when it is dephosphorylated or phosphorylated?
Dephosphorylated by phosphotases.
Pyruvate kinase is inactivated when it is dephosphorylated or phosphorylated?
Phosphorylated.
During exercise, is glycolysis stimulated or not?
Yes. We need to undergo glycolysis so that we can meet the NRG demands our body is asking for,
During excercise, we have elevated levels of _____.
AMP.
When G6P is made, what is its fate?
3 things can happen to G6P:
- Continue with glycolysis.
- Go to liver and store as glycogen if we have enough ATP.
- Go to PPP to make ribose and NADPH.
What happens if we are in a HIGH fed state, but low excercise?
If we are in a high fed state, we have a high amount of glucose. You would think it would continue with glycolysis, right? Wrong.
Bc we are low in excercise, we do not need ATP. So G6P will go to the liver and be stored as glycogen.
We do, after all, need to do something with the extra glucose inour body.
What are the 4 fates of pyruvate?
4 things can happen to pyruvate:
- Aerobic respiration–> go through TCA… to made alot of ATP.
- Anaerobic respiration–> converted into lactate and eventually go through the Cori cycle
- In yeasts and microorganism, it is converted to ethanol.
- Converted to alanine in gluconeogenesis
Why does alanine inhibit pyruvate?
Because pyruvate is converted to alanine in gluconeogenesis.
Problems with glycolysis often result in:
Hemolytic anemias
What is hemolytic anemia?
Hemolytic anemias occur when there is a problem with glycolysis. Our RBC need ATP and when there is a problem with ATP, it fucks with the ion concentrations of RBC. The RBCs will then denature.
What is the most affected enzyme that can cause hemolytic anemia?
Pyruvate kinase (95% of cases)
To remember this, RMBR that it is an enzyme in glycolysis because problems with glycolysis result in hemolytic anemia.
When there is a defect in glycolysis, what is most affected?
RBC (cells that lack MT) and brain!
Why does the brain depend on glucose for NRG?
because glucose is the only thing that can cross the blood, brain barrier
When starving, how does the brain get energy?
- gluconeogenesis.
2. In episodes of EXTREME starvation- the brain will rely on ketone bodies.
In a fed state, we have ____ rates of glycogen production and _____ rates of gluconeogenesis
- increased
2. decrease
Fasting state of glycolysis, less/more catabolism will occur than in fed.
More. Because less is stored and we want to break down our glucose stroages
in a fasting state, we see _____ rates of gluconeogenesis and glycogenolysis
increase
More catabolism occurs in our fed/fasting state?
Fasting
What controls our fed and fasting states?
insulin and glucagon.
Diabetes is characterized by a high amount of _______
glucose- hyperglycemia
Type 1 Diabetes
our bodies are low in insulin, so we take shots
Type 2 diabetes
Worse. our bodies do not respond to insulin so we eventually lose our pancreatic b cells.
Dz as a result of glycolysis disruption:
- Diabetes
- Hemolytic anemia
- Tauri disease
Tauri disease
Tauri disease is a glycogen storing disease. We get Tauri dz when PFK-1 enzyme is fucked up.
As a result of Tauri disease, it causes weakness and cramps because we are not getting the ATP from glycolysis.
